title: Supramolecular assemblies based on complexes of nonionic amphiphilic cyclodextrins and a meso-tetra(4-sulfonatophenyl)porphine tributyltin(IV) derivative: potential nanotherapeutics against melanoma.
abstract: Amphiphilic cyclodextrin (ACyD) provides water-soluble and adaptable nanovectors by modulating the balance between the hydrophobic and hydrophilic chains at both CyD sides. This work aimed to design nanoassemblies based on nonionic and hydrophilic ACyD (SC6OH) for the delivery of a poor-water-soluble organotin(IV)-porphyrin derivative [(Bu3Sn)4TPPS] to melanoma cancer cells. To characterize the porphyrin derivatives under simulated physiological conditions, a speciation was performed using complementary techniques. In aqueous solution (≤ 20 μM), (Bu3Sn)4TPPS primarily exists as a monomer (2 in Figure 1), as suggested by the low static anisotropy (ρ ≈ 0.02) with a negligible formation of porphyrin supramolecular aggregates. MALDI-TOF spectra indicate the presence of moieties (i.e., [(Bu3Sn)3TPPS](-)) that are derivatives of the monomeric species. Spectrofluorimetry coupled with potentiometric measurements primarily assesses the presence of the hydrolytic [(Bu3Sn)4TPPS (OH)4](4-) species under physiological conditions. Nanoassemblies of (Bu3Sn)4TPPS/SC6OH were prepared by dispersion of organic films in PBS at pH 7.4 and were investigated using a combination of spectroscopic and morphological techniques. The UV-vis and emission fluorescence spectra of the (Bu3Sn)4TPPS/SC6OH reveal shifts in the peculiar bands of the organotin(IV)-porphyrin derivative due to its interaction with the ACyD supramolecular assemblies in aqueous solution. The mean size was within the range of 100-120 nm. The ξ-potential was negative (-16 mV) for the (Bu3Sn)4TPPS/SC6OH nanoassemblies, with an entrapment efficiency of approximately 67%. The intracellular delivery, cytotoxicity, nuclear morphology and cell growth kinetics were evaluated via fluorescence microscopy on A375 human melanoma cells. The delivery of (Bu3Sn)4TPPS by ACyD with respect to free (Bu3Sn)4TPPS increases the internalization efficiency and cytotoxicity to induce apoptotic cell death and, at lower concentrations, changes the cellular morphology and prevents cell proliferation.
authors.affiliation: CNR - Istituto per lo Studio dei Materiali Nanostrutturati, UOS Palermo , c/o Dip. Scienze Chimiche dell'Università di Messina, Viale Ferdinando Stagno d'Alcontres 31, 98166 Messina, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Mazzaglia
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Bondì
authors.forename: Angela
authors.initials: A
authors.lastname: Scala
authors.forename: Francesca
authors.initials: F
authors.lastname: Zito
authors.forename: Giovanna
authors.initials: G
authors.lastname: Barbieri
authors.forename: Francesco
authors.initials: F
authors.lastname: Crea
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Vianelli
authors.forename: Placido
authors.initials: P
authors.lastname: Mineo
authors.forename: Tiziana
authors.initials: T
authors.lastname: Fiore
authors.forename: Claudia
authors.initials: C
authors.lastname: Pellerito
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Pellerito
authors.forename: Maria Assunta
authors.initials: MA
authors.lastname: Costa
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003505:Cyclodextrins / Q000008:administration & dosage / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D015394:Molecular Structure; D050997:Nanomedicine; D010316:Particle Size; D013329:Structure-Activity Relationship; D013499:Surface Properties; D013501:Surface-Active Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D014220:Trialkyltin Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D003505:Cyclodextrins; D013501:Surface-Active Agents; D014220:Trialkyltin Compounds